A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy.
A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy.
复制标题
肿瘤来源的III型富含胶原的ECM小生境调节肿瘤细胞休眠。
DOI：
10.1038/s43018-021-00291-9
复制
发表时间：
2022-01
期刊：
影响因子：
22.7
通讯作者：
Bravo-Cordero JJ
中科院分区：
文献类型：
--
作者：
Di Martino JS;Nobre AR;Mondal C;Taha I;Farias EF;Fertig EJ;Naba A;Aguirre-Ghiso JA;Bravo-Cordero JJ
癌细胞在远处器官中传播和播种，在形成临床可检测的转移之前，它们可以在那里保持休眠多年。在这里，我们研究了播散性肿瘤细胞（DTC）如何感知和重塑细胞外基质（ECM）以维持休眠。ECM蛋白质组学揭示休眠癌细胞组装III型胶原富集的ECM小生境。肿瘤来源的III型胶原蛋白是维持肿瘤休眠所必需的，因为其破坏通过DDR 1介导的STAT 1信号传导恢复肿瘤细胞增殖。二次谐波产生双光子显微镜进一步揭示了休眠到再激活的转变伴随着III型胶原结构和丰度的变化。临床样本分析显示，与淋巴结阳性患者相比，淋巴结阴性头颈部鳞状细胞癌（HNSCC）患者的肿瘤中III型胶原蛋白水平升高。我们的数据支持，这些机制的操纵可以作为一个障碍，通过DTC休眠诱导转移。Bravo-Cordero及其同事证明，播散性肿瘤细胞通过分泌胶原蛋白III重塑细胞外基质，并通过DDR 1和STAT 1信号传导产生有利于休眠的基质结构。
Cancer cells disseminate and seed in distant organs, where they can remain dormant for many years before forming clinically detectable metastases. Here we studied how disseminated tumor cells (DTCs) sense and remodel the extracellular matrix (ECM) to sustain dormancy. ECM proteomics revealed that dormant cancer cells assemble type III collagen-enriched ECM niche. Tumor-derived type III collagen is required to sustain tumor dormancy as its disruption restores tumor cell proliferation through DDR1-mediated STAT1 signaling. Second harmonic generation two-photon microscopy further revealed that the dormancy-to-reactivation transition is accompanied by changes in type III collagen architecture and abundance. Analysis of clinical samples revealed that type III collagen levels were increased in tumors from lymph node-negative head and neck squamous cell carcinoma (HNSCC) patients compared to lymph node-positive patients. Our data supports that the manipulation of these mechanisms could serve as a barrier to metastasis through DTCs dormancy induction. ‘Bravo-Cordero and colleagues demonstrate that disseminated tumor cells remodel the extracellular matrix by secreting Collagen III and generate a stromal architecture that favors dormancy through DDR1 and STAT1 signaling
登录
查看更多内容
DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
--
作者：
Bredfeldt JS;Liu Y;Conklin MW;Keely PJ;Mackie TR;Eliceiri KW
通讯作者：
Eliceiri KW
影响因子：
6
作者：
Brisson, Becky K.;Mauldin, Elizabeth A.;Volk, Susan W.
通讯作者：
Volk, Susan W.
影响因子：
6
作者：
Conklin, Matthew W.;Eickhoff, Jens C.;Keely, Patricia J.
通讯作者：
Keely, Patricia J.
影响因子：
5
作者：
Beck, Andrew H.;Espinosa, Inigo;West, Robert B.
通讯作者：
West, Robert B.